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Found: the mother of all blood cells

By Andy Coghlan

The “mother” cell that gives birth to all other blood cells has finally been pinned down after a search lasting more than 20 years.

It’s not that we didn’t know about these mother cells before. Otherwise known as hematopoietic stem cells (HSCs), they are found in the bone marrow and replenish the blood throughout life. For 50 years, they’ve been used to treat people with leukaemia, who receive bone marrow from tissue-matched donors after their own has been destroyed by chemotherapy to kill the cancer.

But isolating individual HSCs has not been easy. “No one has ever gotten a glimpse of them within the mass of cells used when someone gets a transplant,” says John Dick of the University of Toronto in Ontario, Canada, and head of the team which has finally tracked down the mother cells.

“Our work has provided the first sighting, so to speak, of the cell we have known about for many years.”

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All types of blood cell

Dick and his colleagues have now proved that HSCs can regenerate all types of blood cell, including red blood cells, lymphocytes and macrophages.

They did this through a long and painstaking process of transplanting human bone marrow and blood extracts into mice without an immune system, so the human cells wouldn’t be rejected by the animals.

Over many years, Dick and his colleagues narrowed down the search for the elusive cell by deleting each mouse’s bone marrow cells, then replacing mouse marrow with human cells to see whether they would rebuild the entire blood system from scratch.

Eventually, they narrowed their search down to a single cell type, which they also discovered has the CD49f protein on its surface, which marks it out from the rest. When they transplanted bone marrow and blood samples minus the CD49f-marked cells, the blood system failed to regenerate.

The CD49f “biomarker” is vital for further research, because it will enable the genuine HSCs to be extracted from all other blood stem cells, some of which will be at more advanced stages of maturity, and so not capable of turning into all blood types.

New leukaemia treatments

Dick says doctors might be able to safely regenerate a patient’s entire blood system from scratch, using just a small population of the CD49f-marked cell, offering new ways to treat people with leukaemia.

At present, such patients would receive new bone marrow from tissue-matched donors, if available – only a third of patients find a donor. But now it might be possible to reconstitute marrow from HSCs extracted before chemotherapy starts. Checks could be done to make sure the HSCs chosen for regeneration are not themselves cancerous.

Researchers can now also experiment with the HSCs to work out the different stages and steps by which they develop into all types of blood cells, potentially allowing them to make specific blood cells by design.

“This specific HSC marker, CD49f, could not only help to identify which cells are capable of long-term engraftment in patients, but also as a tool to help us generate these cells in the lab from pluripotent stem cell sources,” says Robert Lanza, chief scientist at Advanced Cell Technology in Worcester, Massachusetts. In 2008, the company developed red blood cells from human embryonic stem cells, and hopes soon to begin testing them in patients.